title: Ovarian cancer in BRCA mutation carriers: improved outcome after intraperitoneal (IP) cisplatin.
abstract: BACKGROUND
  Ovarian cancer arising in women with BRCA mutations is known to have a more favorable outcome and to be more responsive to platinum-based regimens than in those without a hereditary background. We analyze our previously published intraperitoneal (IP) studies in relation to BRCA mutation status and update their outcomes.
  
  
  METHODS
  Among 62 patients with ovarian cancer enrolled in IP platinum doublet studies in clinical trials (with etoposide (n = 18), with floxuridine (n = 30), and with topotecan (n = 14)), a deleterious BRCA mutation was eventually identified in 10 patients. The outcomes in these BRCA mutation carriers are described and compared with survival of others in respective trials.
  
  
  RESULTS
  Ten patients that were confirmed to have BRCA mutations-all with high-grade and stages IIC to IV disease-survived a median of 10 years (range: 4-18+) after receiving IP cisplatin-based regimens. Two continue with no evidence of disease since their IP treatment, while four others remain alive with recurrences after 8, 9, 10, and 11 years, respectively.
  
  
  CONCLUSIONS
  This experience suggests that IP cisplatin leads to favorable long term outcomes in advanced ovarian cancer in women with defective homologous recombination (i.e., with deleterious BRCA mutations). Whether such cisplatin dose-intensification from IP relative to (intravenous) IV drug administration leads to superior results in these mutation carriers requires further study.
authors.affiliation: New York University Medical Center, NYU Cancer Institute, New York, NY, USA.
authors.forename: Maryann
authors.initials: M
authors.lastname: Kwa
authors.forename: Susan
authors.initials: S
authors.lastname: Edwards
authors.forename: Andrea
authors.initials: A
authors.lastname: Downey
authors.forename: Elsa
authors.initials: E
authors.lastname: Reich
authors.forename: Robert
authors.initials: R
authors.lastname: Wallach
authors.forename: John
authors.initials: J
authors.lastname: Curtin
authors.forename: Franco
authors.initials: F
authors.lastname: Muggia
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D019313:BRCA1 Protein / Q000235:genetics*; D024682:BRCA2 Protein / Q000235:genetics*; D016190:Carboplatin / Q000008:administration & dosage; D002945:Cisplatin / Q000008:administration & dosage; D017321:Clinical Trials, Phase I as Topic; D017322:Clinical Trials, Phase II as Topic; D018284:Cystadenocarcinoma, Serous / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D005467:Floxuridine / Q000008:administration & dosage; D005500:Follow-Up Studies; D006579:Heterozygote; D006801:Humans; D007274:Injections, Intraperitoneal; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D060787:Neoplasm Grading; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D011379:Prognosis; D015996:Survival Rate; D019772:Topotecan / Q000008:administration & dosage
chemical_list: D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D024682:BRCA2 Protein; C551750:BRCA2 protein, human; D005467:Floxuridine; D005047:Etoposide; D019772:Topotecan; D016190:Carboplatin; D002945:Cisplatin